Pulmonary Arterial Hypertension
Conditions
Keywords
Pulmonary Arterial Hypertension, PAH, WHO Group 1
Brief summary
The primary objective of this study is to assess the safety and tolerance of changing patients currently on bosentan to ambrisentan for the treatment of pulmonary arterial hypertension.
Detailed description
The therapy of pulmonary arterial hypertension (PAH) has been revolutionized with the development and subsequent instruction of oral endothelin receptor antagonists (ERA). The first approved ERA, bosentan (Tracleer, Actelion, Inc.) is an effective drug widely used throughout the world in the therapy of PAH. Newer ERA's, with purported advantages over the first approved drug have since been tested and subsequently been approved for the therapy of PAH in the USA and other countries including ambrisentan (Letairis, Gilead Sciences, Inc.). However, there is little data available on the efficacy, safety and tolerability of the elective change from oral bosentan to oral ambrisentan in PAH.
Interventions
DRUGambrisentan
ambrisentan 2.5mg, 5mg, & 10mg. Daily dosage.
Sponsors
University of Alabama at Birmingham
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients followed routinely in the pulmonary vascular disease clinic at the University of Alabama in Birmingham, greater than or equal to 19 years of age. 2. World Health Organization (WHO) PAH Type I 3. WHO class I-IV symptoms (no functional class exclusion). 4. On bosentan, twice a day, with a maximum daily dose of 250mg, on a stable dose for 3 months with no clinical indication to discontinue the drug (i.e., increased liver function studies or other intolerance). Patients may be on other drug therapies for PAH, and also may be on oxygen therapy (intermittent or continuous).
Exclusion criteria
1. Known intolerance or allergy to ambrisentan. 2. Prior therapy with ambrisentan. 3. Current therapy with two phosphodiesterase-5 inhibitors. 4. Change in other approved therapy for PAH (including phosphodiesterase-5 inhibitors and prostanoids) within 4 weeks of baseline study visit. 5. Planned addition of prostanoid for clinical reasons within 3 months of baseline study visit. 6. Active participation in another clinical study involving the medical therapy of PAH. 7. Uncontrolled systemic hypertension or angina pectoris 8. Serum creatinine greater than 2.5 at or within 4 weeks of baseline. 9. Serum liver function studies greater than 3 x normal at or within 4 weeks of baseline study visit. 10. In the opinion of the investigator, a change in PAH therapy would present significant risk to the subject. 11. In the opinion of the investigator, the participant is unlikely to survive for 12 weeks after study entry. 12. In the opinion of the investigator, the participant is likely to undergo lung or heart-lung transplantation within 12 weeks of study entry. 13. A woman of childbearing potential who is not using an acceptable form of contraception. 14. Pregnancy. 15. In the opinion of the investigator, a participant who is not capable or willing to follow the study procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Not Able to Tolerate Ambrisentan | baseline to 12 weeks | If a subject was not able tolerate ambrisentan, subject was returned to use of bosentan and ambrisentan was withdrawn within first 12 weeks of start. A subject was considered to not be able to tolerate ambrisentan if they experienced an adverse event or side effect that was not acceptable to the subject. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Distance for a Six Minute Walk at 12 Weeks Post Start of Ambrisentan | baseline to 12 weeks | Evaluate the change in exercise tolerance. Measured the distance a subject was capable of walking in 6 minutes at basline compared to the distance at 12 weeks. The distance was measured in meters. A postive result reflects the distance increased at 12 weeks, a negative result reflects how much shorter the distance was. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ambrisentan patients currently on bosentan to ambrisentan for the treatment of pulmonary arterial hypertension.
ambrisentan: ambrisentan 2.5mg, 5mg, & 10mg. Daily dosage. | 28 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Ambrisentan |
|---|---|
| Age, Continuous | 52.6 years STANDARD_DEVIATION 12.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 23 Participants |
| Region of Enrollment United States | 28 participants |
| Sex: Female, Male Female | 26 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 14 / 32 |
| serious Total, serious adverse events | 0 / 32 |
Outcome results
Primary
Number of Subjects Not Able to Tolerate Ambrisentan
If a subject was not able tolerate ambrisentan, subject was returned to use of bosentan and ambrisentan was withdrawn within first 12 weeks of start. A subject was considered to not be able to tolerate ambrisentan if they experienced an adverse event or side effect that was not acceptable to the subject.
Time frame: baseline to 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ambrisentan | Number of Subjects Not Able to Tolerate Ambrisentan | 4 participants |
Secondary
Mean Change in Distance for a Six Minute Walk at 12 Weeks Post Start of Ambrisentan
Evaluate the change in exercise tolerance. Measured the distance a subject was capable of walking in 6 minutes at basline compared to the distance at 12 weeks. The distance was measured in meters. A postive result reflects the distance increased at 12 weeks, a negative result reflects how much shorter the distance was.
Time frame: baseline to 12 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Ambrisentan | Mean Change in Distance for a Six Minute Walk at 12 Weeks Post Start of Ambrisentan | 368.71 meters |